Status:

RECRUITING

NGGT006 Gene Therapy for Homozygous Familial Hypercholesterolemia

Lead Sponsor:

First Affiliated Hospital Xi'an Jiaotong University

Conditions:

Homozygous Familial Hypercholesterolemia

Eligibility:

All Genders

12-55 years

Phase:

EARLY_PHASE1

Brief Summary

This is an early phase 1, open-label, single-center, dose-escalation, pilot trial to evaluate the safety and efficacy of an intravenous infusion of NGGT006 in homozygous familial hypercholesterolemia ...

Detailed Description

Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder of lipoprotein metabolism, characterized by extreme elevations in low-density lipoprotein cholesterol (LDL-C) and leading t...

Eligibility Criteria

Inclusion

  • Voluntarily sign informed consent form;
  • Male or female, 12 ≤ age ≤ 55 years (first patient≥ 18 years), diagnosed as homozygous familial hypercholesterolemia with genetic confirmation of two mutant alleles of the LDL receptor (LDLR) gene;
  • AAV8 neutralizing antibodies can be negative or reduced to negative levels through methods such as plasma exchange.
  • Untreated LDL-C ≥10 mmol/L (386mg/ dL) or treated LDL-C ≥7 mmol/L (270mg/ dL) together with cutaneous or tendon xanthoma before age 18 years;
  • Had been on stable medication for ≥30 days if receiving lipid-lowering therapy (or ≥60 days if receiving alirocumab or evolocumab) prior to screening and not scheduled for addition of new drugs or dose adjustments during the study;
  • Agreed to follow a low-fat diet and comply with all study procedures;
  • Agreed to maintain a similar exercise volume and intensity to baseline during the study period;
  • Agreed to maintain good lifestyle habits;
  • No history of alcohol abuse or alcohol dependence (diagnosed as F10 in ICD-10 code);
  • No sexual activity for 14 days prior to administration and negative serum pregnancy test in female participants;
  • Participants of childbearing potential agreed to use highly effective contraception for at least 365 days from administration of NGGT006;
  • No plan of stent implantation within 3 months.

Exclusion

  • Positive for hepatitis B surface antigen, hepatitis C, human immunodeficiency virus (HIV) or syphilis test;
  • Clinically significant abnormalities in liver function test: alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) and/or aspartate aminotransferase (AST) ≥2 × ULN;
  • Baseline blood pressure ≥160/100 mmHg (1 repeat measurement is allowed);
  • Uncontrolled myocardial infarction or heart failure, or had surgery plan within 1 year;
  • Diabetes diagnosed within 3 months or with poor control (HbA1c ≥9%);
  • Acute or chronic kidney failure;
  • Hemoglobin (Hb) ≥120g/L (male), Hb ≥110 (female);
  • Abnormal platelet counts or morphology;
  • History or laboratory tests suggestive of thrombosis;
  • Had contraindications to glucocorticoid (e.g., epilepsy, severe schizophrenia, active peptic ulcer);
  • Life expectancy less than 1 year;
  • With malignant tumors;
  • Liver fibrosis or liver cancer;
  • Previous gene therapy treatment;
  • Hypersensitivity to AAV or cortisone or immunosuppressants (sirolimus, rituximab, tacrolimus);
  • Participation in any other clinical trial within 3 months;
  • History of stent implantation within 1 month or myocardial infarction within 3 months;
  • Breastfeeding females;
  • Any other condition that may not be appropriate for the study in the opinion of the Investigator.

Key Trial Info

Start Date :

October 29 2023

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

November 1 2028

Estimated Enrollment :

12 Patients enrolled

Trial Details

Trial ID

NCT06125847

Start Date

October 29 2023

End Date

November 1 2028

Last Update

December 9 2024

Active Locations (1)

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Page 1 of 1 (1 locations)

1

First Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, China, 710061